Hebbian rehabilitation for spinal cord injury

Noam Y. Harel; originally posted 8/21/2008; updated 3/31/2013

• Most spinal cord injuries (SCI), even if they cause complete paralysis and sensory loss below the lesion, tend to spare a variable amount of nerve fibers passing through the lesion (Kakulas, 1987).
• Brainstem circuits comprise the majority of spared fibers (Nathan, 1996). However, people with SCI may have difficulty consciously controlling these subcortical circuits.
• The locomotor central pattern generator (CPG), located within the thoraco-lumbar junction of the spinal cord, mediates reflexive walking with only minimal conscious control. The CPG is located below the level of injury in roughly 85% of human SCI patients.
• Currently, gait training rehabilitation for SCI patients often focuses on stimulating the CPG through weight-supported treadmill training. Rehabilitation exercises are not as focused on re-establishing supraspinal voluntary control of the CPG (van den Brand et al., 2012).
• Neural learning is strengthened by simultaneous multisensory input/activation - "Fire Together, Wire Together" (Hebb's Principle).
• Could motor learning (eg SCI rehab) benefit from a similar simultaneous sensorimotor approach? Especially if the approach is aimed higher, above rather than below spinal lesions?

• To strengthen cortical connections to the brainstem circuits that more likely retain spared fibers across spinal injuries.
• This could be achieved using combinations of physical exercises that stimulate brainstem pathways (eg balance exercises-->vestibulospinal, reticulospinal circuits) and cortical pathways (eg skilled hand exercises-->corticospinal tract).
• This should result in formation of detour pathways that re-establish volitional control over subcortical and spinal circuits.
• Strengthened detour pathways should result in improved motor function and electrical transmission across and below spinal injuries.
• We have tested this approach in mice with incomplete injuries (Harel et al., 2010; Harel et al., in preparation).
• We are now testing this approach in humans with incomplete thoracic SCI (see clinicaltrials.gov NCT01740128).
• In mice, we see improved behavioral outcomes with multimodal 'Hebbian' training. We do not see a corresponding increase in anatomical growth of the corticospinal or raphespinal tracts.
• In humans, we are following both functional outcomes and electrophysiological outcomes (using transcranial magnetic stimulation and electromyography).
• We hope to test a similar strategy of combining brainstem-activating balance exercises with cortical-activating direct current stimulation (DCS).